Background: Immune checkpoint inhibitors (ICIs) have limited efficacy in proficient mismatch repair (pMMR) and microsatellite stability (MSS) metastatic colorectal cancer (mCRC). Inhibition of vascular endothelial growth factor (VEGF) or cytotoxic chemotherapy can boost immunogenicity and has the potential to upregulate ICI efficacy. Methods: A comprehensive electronic literature search was conducted up to April 2025 to identify randomized controlled trials comparing cytotoxic chemotherapy plus bevacizumab with or without ICI. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), objective response rate (ORR), and severe adverse events (AEs: grade 3 or more). A meta-analysis was performed using random-effects models to calculate hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Results: Four studies involving 986 patients (With-ICI group,n= 651; Without-ICI group,n= 335) were included. The meta-analysis demonstrated a significant improvement in PFS in the With-ICI group compared with the Without-ICI group, with an HR of 0.82 (95% CI: 0.70–0.96,p= 0.01) without statistical heterogeneity. No significant improvements were observed between the With- and Without-ICI groups in OS and ORR meta-analyses, but the With-ICI group had a favorable trend in OS. A significant increase in serious AEs was not observed in the With-ICI group. Conclusions: This meta-analysis suggests a potential benefit of adding ICIs to chemotherapy plus bevacizumab in pMMR mCRC; however, the evidence remains preliminary and hypothesis-generating, warranting further investigation in biomarker-driven trials and clarification of long-term outcomes.
背景：在错配修复功能正常（pMMR）和微卫星稳定（MSS）的转移性结直肠癌（mCRC）中，免疫检查点抑制剂（ICIs）的疗效有限。抑制血管内皮生长因子（VEGF）或使用细胞毒性化疗可增强免疫原性，并可能提升ICI的疗效。方法：截至2025年4月，进行了全面的电子文献检索，以识别比较细胞毒性化疗联合贝伐珠单抗加或不加ICI的随机对照试验。主要结局指标为无进展生存期（PFS），次要结局指标包括总生存期（OS）、客观缓解率（ORR）以及严重不良事件（AEs：3级或以上）。采用随机效应模型进行荟萃分析，计算风险比（HRs）或比值比（ORs）及其95%置信区间（CIs）。结果：共纳入4项研究，涉及986例患者（ICI组，n=651；非ICI组，n=335）。荟萃分析显示，与非ICI组相比，ICI组的PFS有显著改善，HR为0.82（95% CI: 0.70–0.96, p=0.01），且无统计学异质性。在OS和ORR的荟萃分析中，ICI组与非ICI组之间未观察到显著改善，但ICI组在OS方面显示出有利趋势。未观察到ICI组严重AEs显著增加。结论：本荟萃分析表明，在pMMR mCRC中，化疗联合贝伐珠单抗的基础上加用ICIs可能带来获益；然而，证据仍属初步且为假设生成性质，需要在生物标志物驱动的试验中进一步研究，并明确长期结局。
肿瘤(癌症)患者之家